Although hormone therapy still is approved for relief of moderate to severe menopausal vasomotor symptoms in eligible women, its association with breast cancer, stroke, and heart disease in recent studies has led to greater interest in nonhormonal treatments. More than 60 percent of women 45 to 65 years of age are reported to believe that “natural” therapies are superior to hormone medications, and at least 22 percent of menopausal women, one study found, have used “alternative” therapies for symptoms such as hot flashes, night sweats, and vaginal dryness. A survey of women attending specialized clinics found that nearly 80 percent used botanical dietary supplements but less than one third informed their physicians of this use. Krebs and colleagues conducted a systematic review of the literature concerning the effectiveness and tolerability of the most frequently used phytoestrogen products.

The authors identified 40 clinical trials from MEDLINE searches, bibliographies of trials and reviews, and searches of relevant journals and conference abstracts. These trials were then reviewed for quality in design and conduct, specifically reporting of inclusion criteria, type and dose of phytoestrogen used, outcome measures, adverse effects, reasons for discontinuation or loss to follow-up, and trial sponsorship. Twenty-two trials with a total of 2,069 participants fulfilled criteria for inclusion in the study. Six of these were conducted in the United States. The number of participants in the studies ranged from 24 to 252, with a mean age of 53 years and an average menopause duration of 4.3 years. In the five trials that reported race, most participants (75 percent) were white. All trials compared phytoestrogen with placebo rather than hormone therapy. Trial duration ranged from four to 104 weeks, and the average drop-out rate was 15.5 percent.

Ten studies with a combined total of 995 participants and one abstract with 99 participants investigated soy products. The daily isoflavone intake was between 34 and 134 mg per day. Seven of the eight trials that documented frequency of hot flashes showed no improvement in the study group compared with the control group. Only two studies reported any favorable results, and these were in subscales of subjective symptom questionnaires. The seven trials and two abstracts involving soy extracts all used different products and had mixed results, even when the same outcomes, such as the Kupperman index, were assessed.

Five trials with a total of 400 participants studied the effects of red clover on menopausal symptoms. The frequency of hot flashes was reduced among women taking red clover in two of these trials, but no overall improvement in symptoms was documented. Two studies of flaxseed did not report statistical comparisons between the groups.

Information about adverse effects was reported in 12 trials. In two of the trials involving soy products, adverse gastrointestinal effects were reported by women taking soy products (47 and 75 percent); and in one of these trials, one fourth of patients taking soy discontinued the study because of the taste of the product. Estrogenic side effects such as breast tenderness and vaginal bleeding were rare with soy products or extracts.

The authors conclude that phytoestrogen products are no more effective than placebo in relieving menopausal symptoms, regardless of the type or dose of phytoestrogen used.